Controlled release of IGF‐I from a biodegradable matrix improves functional recovery of skeletal muscle from ischemia/reperfusion

Abstract

Ischemia/reperfusion (I/R) injury is a considerable insult to skeletal muscle, often resulting in prolonged functional deficits. The purpose of the current study was to evaluate the controlled release of the pro-regenerative growth factor, insulin-like growth factor-I (IGF-I), from a biodegradable polyethylene glycol (PEG)ylated fibrin gel matrix and the subsequent recovery of skeletal muscle from I/R. To accomplish this, the hind limbs of male Sprague–Dawley rats were subjected to 2-h tourniquet-induced I/R then treated with saline, bolus IGF-I (bIGF), PEGylated fibrin gel (PEG-Fib), or IGF-I conjugated PEGy-lated fibrin gel (PEG-Fib-IGF). Functional and histological evaluations were performed following 14 days of reperfusion, and muscles from 4-day reperfusion animals were analyzed by Western blotting and histological assessments. There was no difference in functional recovery between saline, bIGF, or PEG-Fib groups. However, PEG-Fib-IGF treatment resulted in significant improvement of muscle function and structure, as observed histologically. Activation of the PI3K/Akt pathway was significantly elevated in PEG-Fib-IGF muscles, compared to PEG-Fib treatment, at 4 days of reperfusion, suggesting involvement of the pathway PI3K/Akt as a mediator of the improved function. Surprisingly, myoblast activity was not evident as a result of PEG-Fib-IGF treatment. Taken together, these data give evidence for a protective role for the delivered IGF. These results indicate that PEG-Fib-IGF is a viable therapeutic technique in the treatment of skeletal muscle I/R injury.

Regulating myogenic differentiation of mesenchymal stem cells using thermosensitive hydrogels

“…Hydrogels are one type of matrix widely used to deliver cells for muscle regeneration [36]. These include collagen [37], alginate [38], fibrin [35,39], hyaluronic acid [40], and poly(ethylene glycol) [41]. Hydrogel modulus may be used to induce stem cell myogenic differentiation.…”

“…A potential approach to increase myogenic differentiation is to deliver stem cells using suitable matrix, where matrix property itself and/or loaded biomolecules induce myogenic differentiation [34,35]. Hydrogels are one type of matrix widely used to deliver cells for muscle regeneration [36].…”

The Potential of Combination Therapeutics for More Complete Repair of Volumetric Muscle Loss Injuries: The Role of Exogenous Growth Factors and/or Progenitor Cells in Implantable Skeletal Muscle Tissue Engineering Technologies

“…Growth factor concentrations varied significantly across the studies as well as for the individual growth factors used (VEGF: 1-3 μg; IGF: 6-10 μg; bFGF: 5 ng to 100 μg; HGF: 5 ng to 100 μg). Table 2 also highlights the relatively small number of studies (4/12 studies) that reported the degree of functional regeneration after treatment (rather than just tissue reconstitution), and 3 of them were conducted in hind limb ischemia injury models [Borselli et al, 2010;Hammers et al, 2012;Rybalko et al, 2015b]. There was only 1 study (1/12) in which growth factor-based repair studies evaluated functional recovery in a VML injury model [Grasman et al, 2015].…”

Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

“…A wide range of cytokines, growth factors and other bioactive molecules have been found to be essential for supporting the viability and differentiation of stem cells alongside the skeletal myogenic lineage. The most effective bioactive molecules in this context are myogenic growth factor IGF-1 and angiogenic growth factor VEGF; they both have been reported to positively influence muscle cell populations in vitro and in vivo [71,72,123,135].…”